Inherent in this proposal is the hypothesis that connective tissue plays an important role in influencing cell behavior and should not be considered in its traditional role as simply a mechanical support for cells. Much evidence has begun to accumulate supporting an active role for connective tissue in influencing cell activities. The recent discoveries of genetically distinct collagen types suggest that each collagen molecule must play a unique role in growth and development. It is our belief that collagen plays an important role in tumor formation, growth, and metastasis. Therefore, the goal of this proposal is to establish the role and relationship of matrix, particularly collagen, to tumor growth and metastasis. The first objective is to establish the structure, organization, function and metabolism of collagen in tumors, and malignantly transformed cells. The amount, type and structural characteristics of each genetically distinct molecule will be quantitated and compared to similar but normal tissues and cells. This should provide a biochemical marker for characterizing solid tumors and may be useful in predicting their growth and spread. Second objective will be to establish whether the collagen stroma is formed by tumor cells or is a last response to the tumor. Finally the cell-collagen interactions will be studied to determine if tumor cells have less cellular anchorage to collagen in a primary cell mass and whether secondary metastasis in specific organs is a result of favorable cell-matrix reactions.